AB1254 ECTOPIC ARTICULAR CALCIFICATIONS AND ARTERIAL OCCLUSIVE DISEASE DUE TO 5-NUCLEOTIDASE DEFICIENCY
Authors: M. Maffi, G. De Mattia, M. Mosca, M. Mazzantini
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Calcification of Joints and Arteries (CALJA) is a rare disease presenting with recurrent/chronic arthritis and <i>claudicatio intermittens</i> of the lower limbs. Since the discovery of specific mutations of the <i>5'-nucleotidase</i> (<i>NT5E</i>) gene responsible for the disease, only few cases have been reported. <h3>Objectives</h3> To collect available information about CALJA to better characterize the disease and to raise awareness of this often unrecognized rheumatologic condition. <h3>Methods</h3> All available publications regarding CALJA since its first description in 2011 were included and a case report is described. <h3>Results</h3> A 65-year-old woman, affected by seronegative oligoarthritis since 2007, reported lower limb claudication. In 2021 past medical history consisted of migratory, non-erosive arthritis with asymmetrical involvement of peripheral joints since the age of 30, poorly responsive to glucocorticoids and immunosuppressive therapy. She had never presented any clinical sign of connective tissue disease or microcrystalline arthritis, as shown in X-rays performed in 2007/2010. In November 2021, because of the worsening of the claudication, an arterial color Doppler ultrasound of the lower limbs was performed, which revealed bilateral obliteration of superficial femoral artery, of posterior and anterior tibial arteries, and of lateral plantar arteries. X-rays showed extensive calcifications of the femoral and popliteal arteries as well as widespread articular and periarticular calcific deposits, with the appearance of hydroxyapatite deposits. Laboratory findings included inflammatory markers elevation, whereas calcium-phosphorus metabolism, lipid and glucose profile, blood count, and renal/hepatic function were normal. She had never smoked and had no significant cardiovascular risk factors. Based on the knowledge of a very rare genetic condition called <b>CAL</b>cification of <b>J</b>oints and <b>A</b>rteries (<i>CALJA,</i> MIM 211800), <i>ecto-5'-nucleotidase (NT5E</i>) gene analysis was performed, which resulted positive for the homozygous inactivating variant NM_002526.3:c.751(1G&gt;A). NT5E activity leads to adenosine production, which in turn inhibits Tissue Non-specific Alkaline Phosphatase (TNAP) synthesis. TNAP degrades PPi into inorganic phosphate, an activator of calcification; therefore, inactivation of NT5E leads to vascular (lower limbs) and periarticular calcification in CALJA patients, with the clinical features of progressive arterial disease and microcrystalline arthritis. To date, 23 patients with CALJA had been reported (<i>Table 1</i>). Seventeen patients are female (74%), mean age at diagnosis is 59-year-old and the most common symptoms are intermittent claudication (87%) and joint pain due to periarticular calcification (70%); upper extremities arterial calcifications (9%) and calcific aortic valve stenosis (17%) are less commonly described. <h3>Conclusion</h3> To our knowledge, this patient is the first case of CALJA with variant NM_002526.3:c.751(1G&gt;A) of <i>NT5E</i>. Patients presenting with CALJA are often treated with immunosuppressive agents in the suspicion of inflammatory rheumatologic diseases. Thus, it is important for the Rheumatologist to recognize the features of this disease and to keep it in mind in the differential diagnosis of patients suffering from arthritis and/or early osteoarthritis along with lower limb arterial insufficiency. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.